Osteoarthritis cartilage histopathology: grading and staging

Pritzker, Kenneth P.H.; Jimenez, Sergio A.; Østergaard, Keld; Pelletier, J.-P.; Revell, Peter A.; Salter, Donald; Berg, Wim B. van den

doi:10.1016/j.joca.2005.07.014

Cited by 1,891 publications

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“…5B), similar to the RBPjκ insufficiency. Quantification by grading systems (25) confirmed that the DAPT injection significantly suppressed OA development (Fig. 5C).…”

Section: Notch Signaling Enhances the Terminal Stage Of Endochondralmentioning

confidence: 58%

“…This suppression was associated with the decreases in expressions of Mmp13, Vegfa, and Hes1, but not Col10a1, indicating prevention of the terminal stage of endochondral ossification by the RBPjκ insufficiency, similar to the Sox9-Cre;Rbpj fl/fl limb cartilage. Quantification by grading systems (25) confirmed that the RBPjκ insufficiency caused significant resistance to OA development (Fig. S1E).…”

Section: Notch Signaling Molecules Are Expressed and Activated Duringmentioning

confidence: 62%

“…Tamoxifen (Sigma; 100 μg per gram of body weight) was intraperitoneally injected to 7-wk-old Col2a1-Cre ERT ;Rbpj fl/fl mice and the Rbpj fl/fl littermates daily for 5 d. We then performed the surgical procedure to create an experimental OA model on 8-wk-old male mice as previously reported (24), and we analyzed them 8 wk after surgery. We quantified OA severity by the OARSI system (25), which was assessed by a single observer who was blinded to the experimental group.…”

Section: Methodsmentioning

confidence: 99%

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Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development

Hosaka¹,

Saito

Sugita³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

160

165

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Here we examined the involvement of Notch signaling in the endochondral ossification process, which is crucial for osteoarthritis (OA) development. Intracellular domains of Notch1 and -2 were translocated into the nucleus of chondrocytes with their differentiation in mouse limb cartilage and in mouse and human OA articular cartilage. A tissue-specific inactivation of the Notch transcriptional effector recombination signal binding protein for Ig kappa J (RBPjκ) in chondroprogenitor cells of SRY-box containing gene 9 (Sox9) -Cre ;Rbpj fl/fl mouse embryos caused an impaired terminal stage of endochondral ossification in the limb cartilage. The RBPjκ inactivation in adult articular cartilage after normal skeletal growth using type II collagen ( Col2a1 )- Cre ERT ;Rbpj fl/fl mice by tamoxifen injection caused resistance to OA development in the knee joint. Notch intracellular domain with the effector RBPjκ stimulated endochondral ossification through induction of the target gene Hes1 in chondrocytes. Among the Notch ligands, Jagged1 was strongly induced during OA development. Finally, intraarticular injection of N -[ N -(3,5-diflurophenylacetate)- l -alanyl]-(S)-phenylglycine t-butyl ester (DAPT), a small compound Notch inhibitor, to the mouse knee joint prevented OA development. The RBPjκ-dependent Notch signaling in chondrocytes modulates the terminal stage of endochondral ossification and OA development, representing an extracellular therapeutic target of OA.

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“…5B), similar to the RBPjκ insufficiency. Quantification by grading systems (25) confirmed that the DAPT injection significantly suppressed OA development (Fig. 5C).…”

Section: Notch Signaling Enhances the Terminal Stage Of Endochondralmentioning

confidence: 58%

Section: Notch Signaling Molecules Are Expressed and Activated Duringmentioning

confidence: 62%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development

Hosaka¹,

Saito

Sugita³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

160

165

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“…The OARSI cartilage OA pathology assessment system provides six grades of OA involvement (46). In grade 1, the cartilage matrix undergoes swelling, abrasion and changes in the structure of the cartilage such as patchy condensation of collagen and gain or loss of chondrocytes.…”

Section: Features Of Articular Cartilage During Osteoarthritismentioning

confidence: 99%

Sodium and T_1ρ MRI for molecular and diagnostic imaging of articular cartilage

et al. 2006

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In this article, both sodium magnetic resonance (MR) and T 1r relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T 1r , a brief description of (i) principles of measuring T 1r relaxation, (ii) pulse sequences for computing T 1r relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T 1r in biological tissues and (v) effects of exchange and dipolar interaction on T 1r dispersion are discussed. Correlation of T 1r relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokineinduced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T 1r data from osteoarthritic specimens, animal models, healthy human subjects and as well from osteoarthritic patients are provided. The current status of T 1r relaxation mapping of cartilage and future directions is also discussed. Copyright # 2006 John Wiley & Sons, Ltd. KEYWORDS: cartilage; arthritis; spin-lock; T1rho; sodium; MRI OSTEOARTHRITIS Osteoarthritis (OA) affects more than half of the population above the age of 65 (1,2) and has a significant negative impact on the quality of life of elderly individuals (3). The economic costs in the USA from OA have been estimated to be more than 1% of the gross domestic product (4). OA is now increasingly viewed as a metabolically active joint disorder of diverse etiologies. The biochemistry of the disease is characterized by the following changes in cartilage: reduced proteoglycan (PG) concentration, possible changes in the size of collagen fibril and aggregation of PG, increased water content and increased rate of synthesis and degradation of matrix macromolecules. The earliest changes in the cartilage due to OA result in a partial breakdown in the proteoglyc...

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“…Histological sections were numbered to obscure treatments and examined by two independent reviewers and scored using the OARSI scoring system. 33 The OARSI scoring system produced a score between 0 and 24 that was the mathematical product of the lesion grade and stage. Grade (0-6) indicated depth of the lesion where lesion stage corresponds to the area of abnormal cartilage as determined by India ink staining and histological examination of multiple (12)(13)(14)(15) sections of the femoral condyle.…”

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confidence: 99%

BMP‐7 protects against progression of cartilage degeneration after impact injury

Hurtig

Chubinskaya

Dickey

et al. 2008

Journal Orthopaedic Research

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In vivo studies were used to characterize a model of cartilage injury leading to osteoarthritis progression in the medial femorotibial joint of sheep. In three subsequent studies, bilateral impact injuries were created and one joint received intraarticular injections of 340 mg of rhBMP-7 protein in a collagen particle carrier while the contralateral knee received the vehicle alone. Sheep were allocated to three groups that received intraarticular injections on day 0 (group A), 21 (group B), or 90 (group C) after experimental knee injury. In each group the, joints were evaluated for signs of osteoarthritis progression 90 days after the last treatment using India ink stained area, OARSI histological scoring, cartilage sGAG content, immunostaining for apoptosis (TUNEL), caspase-3, collagen degradation (Col 2 3/4C short collagen epitope), and the endogenous (pro-) form of BMP-7 protein. Knee joints that received rhBMP-7 immediately after injury had small focal lesions at the injury site that did not progress into the surrounding cartilage. Joints that received BMP-7 3 weeks after injury were improved and had limited progression compared to controls, but joints that received the protein 12 weeks after injury had no statistically significant improvement. These studies suggest that BMP-7 may be chondroprotective after traumatic injury in patients if it is administered within 3 to 4 weeks of the index injury. The mechanism of protection after sublethal injury appeared to be an increased survival of chondrocytes that are able to participate in the repair process. ß

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Osteoarthritis cartilage histopathology: grading and staging

Abstract: The OARSI cartilage OA histopathology grading system appears consistent and simple to apply. Further studies are required to confirm the system's utility.

Cited by 1,891 publications

References 45 publications

Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development

Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development

Sodium and T_1ρ MRI for molecular and diagnostic imaging of articular cartilage

BMP‐7 protects against progression of cartilage degeneration after impact injury

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Osteoarthritis cartilage histopathology: grading and staging

Abstract: The OARSI cartilage OA histopathology grading system appears consistent and simple to apply. Further studies are required to confirm the system's utility.

Cited by 1,891 publications

References 45 publications

Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development

Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development

Sodium and T1ρ MRI for molecular and diagnostic imaging of articular cartilage

BMP‐7 protects against progression of cartilage degeneration after impact injury

Contact Info

Product

Resources

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Sodium and T_1ρ MRI for molecular and diagnostic imaging of articular cartilage